Although cholinergic hyperresponsiveness and beta-adrenergic hyporesponsiveness in bronchial asthma is well documented, the role of the histamine receptors system is not known. We propose to study the specific role played by H1 and H2 histamine receptors in allergic asthma and their direct (smooth muscle) and indirect (vagal reflex) effects. Allergic sheep with reproducible bronchoconstriction to an aerosol of Ascaris suum antigen will serve as a model of bronchial asthma, and their airway responses will be compared to a group of normal (non-allergic) sheep. Airway responses to histamine and antigen challenge will be estimated by measurement of static and dynamic resiratory mechanics, and arterial blood gas composition; in addition, to evaluate direct and reflex effects of histamine, unilateral lung resistance will be measured in tracheostomized sheep. The proposed investigation is based upon the hypothesis that a) H2-histamine receptors are functionally depressed in allergic asthma, b) the inter-individual variation in airway responsiveness to histamine is related to differences in airway H2-histamine receptor function, c) the mode of action of histamine is altered in asthma, so that the ratio of reflex to direct effect of histamine is altered in favor of reflex effect. Different pulmonary functions will be measured after inhalation of histamine, H1 and H2 agonists and Ascaris suum antigen, without and with selective H1 and H2 antagonists pretreatment. Effects of unilateral histamine inhalation on ipsi- and contralateral lung function will be evaluated with and without vagal cooling and H1 blockade. We expect that the information derived from these experiments will contribute to the understanding of the role of histamine receptors in allergic bronchial asthma, this could serve as basis for pharmacological intervention.